Differential expression of bone morphogenetic protein 4-6 (BMP-4, -5, and -6) and growth differentiation factor-9 (GDF-9) during ovarian development in neonatal pigs.
ABSTRACT Growth differentiation factor-9 (GDF-9) and bone morphogenetic proteins (BMPs), comprise the largest subgroups of ligands in the TGF-beta superfamily, and have been shown to be involved in follicle development in mammals. However, whether these factors are involved in folliculogenesis in pigs is still unknown. The present study was performed to determine the relationships between early folliculogenesis and the expression of GDF-9 and BMP (BMP-4, -5 and -6) mRNAs in neonatal pigs. Ovaries were removed at 5, 16, 28 and 39 days after birth to examine the follicular population (the right ovary of each animal) and to detect mRNA expression (the left ovary of each animal). Primordial follicles accounted for >80% of the ovarian follicles from 5 days until 39 days after birth. A marked increase in primary follicles and the appearance of secondary follicles were observed in the ovaries at 28 days after birth. BMP-4, -5, and -6 and GDF-9 mRNAs were expressed by ovaries at 5-, 16-, 28- and 39-day-old pigs. The peak expression of BMP-4, -5, and -6 and GDF-9 mRNAs was observed in the ovaries at 5, 39, 28 and 16 days, respectively, after birth. These data demonstrate that folliculogenesis in piglets might be controlled by the interaction with these factors. We conclude that BMPs and GDF-9 may have distinct functions in several stages of follicle development in neonatal pig ovaries.
- Genes & Development 08/1996; 10(13):1580-94. · 12.44 Impact Factor
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ABSTRACT: In addition to pituitary gonadotropins and paracrine factors, ovarian follicle development is also modulated by oocyte factors capable of stimulating granulosa cell proliferation but suppressing their differentiation. The nature of these oocyte factors is unclear. Because growth differentiation factor-9 (GDF-9) enhanced preantral follicle growth and was detected in the oocytes of early antral and preovulatory follicles, we hypothesized that this oocyte hormone could regulate the proliferation and differentiation of granulosa cells from these advanced follicles. Treatment with recombinant GDF-9, but not FSH, stimulated thymidine incorporation into cultured granulosa cells from both early antral and preovulatory follicles, accompanied by increases in granulosa cell number. Although GDF-9 treatment alone stimulated basal steroidogenesis in granulosa cells, cotreatment with GDF-9 suppressed FSH-stimulated progesterone and estradiol production. In addition, GDF-9 cotreatment attentuated FSH-induced LH receptor formation. The inhibitory effects of GDF-9 on FSH-induced granulosa cell differentiation were accompanied by decreases in the FSH-induced cAMP production. These data suggested that GDF-9 is a proliferation factor for granulosa cells from early antral and preovulatory follicles but suppresses FSH-induced differentiation of the same cells. Thus, oocyte-derived GDF-9 could account, at least partially, for the oocyte factor(s) previously reported to control cumulus and granulosa cell differentiation.Biology of Reproduction 03/2000; 62(2):370-7. · 4.03 Impact Factor
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ABSTRACT: Folliculogenesis is regulated by the interplay of extraovarian and intraovarian factors, and the importance of each type of regulation varies depending on the developmental stage of the follicle. Preantral follicle development is regulated predominantly by factors produced locally within the ovary and within the follicle itself. The oocyte has been shown to produce soluble factor(s), which regulate a number of processes in follicular development, including cumulus expansion in the periovulatory period. Members of the TGFβ superfamily are potent regulators of cell proliferation and differentiation in a number of organ systems, and three members, growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15) and BMP-6 are expressed by the oocyte and may mediate effects attributed to the oocyte. Based on knockout mouse models BMP-6 does not play an essential role in ovarian function, but GDF-9 is absolutely required for preantral follicle development. GDF-9 also alters the periovulatory expression of granulosa cell genes and stimulates cumulus expansion. Although BMP-15 is expressed identically to GDF-9, its role in regulating ovarian function is still unknown. This review examines the similarities and differences in sequence, expression, and function of the oocyte-expressed TGFβ family members with respect to regulating folliculogenesis.Molecular and Cellular Endocrinology - MOL CELL ENDOCRINOL. 01/2000; 159(1):1-5.